tbuckley/cabot-search huggingface dataset:
Germline genetic variants are associated with development of insulin-dependent diabetes in cancer patients treated with immune checkpoint inhibitors
Authors: Jasmine I Caulfield, Lilach Aizenbud, Ana Luisa Perdigoto, Eric Meffre, Lucia Jilaveanu, Dominika A Michalek, Stephen S Rich, Yariv Aizenbud, Adebowale Adeniran, Kevan C Herold, Matthew R Austin, Harriet Kluger
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Immune checkpoint inhibitors (ICIs) have dramatically improved survival in patients with cancer but are often accompanied by severe immune-related adverse events (irAEs), which can sometimes be irreversible. Insulin-dependent diabetes is a rare, but life-altering irAE. Our purpose was to determine whether recurrent somatic or germline mutations are observed in patients who develop insulin-dependent diabetes as an irAE. Methods We performed RNA and whole exome sequencing on tumors from 13 patients who developed diabetes due to ICI exposure (ICI-induced diabetes mellitus, ICI-DM) compared with control patients who did not develop diabetes. Results In tumors from ICI-DM patients, we did not find differences in expression of conventional type 1 diabetes autoantigens, but we did observe significant overexpression of ORM1, PLG, and G6PC, all of which have been implicated in type 1 diabetes or are related to pancreas and islet cell function. Interestingly, we observed a missense mutation in NLRC5 in tumors of 9 of the 13 ICI-DM patients that was not observed in the control patients treated with the same drugs for the same cancers. Germline DNA from the ICI-DM patients was sequenced; all NLRC5 mutations were germline. The prevalence of NLRC5 germline variants was significantly greater than the general population (p=5.98×10 −6 ). Although NLRC5 is implicated in development of type 1 diabetes, germline NLRC5 mutations were not found in public databases from patients with type 1 diabetes, suggesting a different mechanism of insulin-dependent diabetes in immunotherapy-treated patients with cancer. Conclusions Validation of the NLRC5 mutation as a potential predictive biomarker is warranted, as it might improve patient selection for treatment regimens. Furthermore, this genetic alteration suggests potential mechanisms of islet cell destruction in the setting of checkpoint inhibitor therapy.
Anti-VEGF therapy improves EGFR-vIII-CAR-T cell delivery and efficacy in syngeneic glioblastoma models in mice
Authors: Xinyue Dong, Jun Ren, Zohreh Amoozgar, Somin Lee, Meenal Datta, Sylvie Roberge, Mark Duquette, Dai Fukumura, Rakesh K Jain
Journal: Journal for ImmunoTherapy of Cancer (2023)

Chimeric antigen receptor (CAR)-T cells have revolutionized the treatment of multiple types of hematological malignancies, but have shown limited efficacy in patients with glioblastoma (GBM) or other solid tumors. This may be largely due to the immunosuppressive tumor microenvironment (TME) that compromises CAR-T cells’ delivery and antitumor activity. We previously showed that blocking vascular endothelial growth factor (VEGF) signaling can normalize tumor vessels in murine and human tumors, including GBM, breast, liver, and rectal carcinomas. Moreover, we demonstrated that vascular normalization can improve the delivery of CD8+ T cells and the efficacy of immunotherapy in breast cancer models in mice. In fact, the US FDA (Food and drug administration) has approved seven different combinations of anti-VEGF drugs and immune checkpoint blockers for liver, kidney, lung and endometrial cancers in the past 3 years. Here, we tested the hypothesis that anti-VEGF therapy can improve the delivery and efficacy of CAR-T cells in immunocompetent mice bearing orthotopic GBM tumors. We engineered two syngeneic mouse GBM cell lines (CT2A and GSC005) to express EGFRvIII—one of the most common neoantigens in human GBM—and CAR T cells to recognize EGFRvIII. We found that treatment with the anti-mouse VEGF antibody (B20) improved CAR-T cell infiltration and distribution throughout the GBM TME, delayed tumor growth, and prolonged survival of GBM-bearing mice compared with EGFRvIII-CAR-T cell therapy alone. Our findings provide compelling data and a rationale for clinical evaluation of anti-VEGF agents with CAR T cells for GBM patients.
Targeting the chromatin effector Pygo2 promotes cytotoxic T cell responses and overcomes immunotherapy resistance in prostate cancer
Authors: Yini Zhu, Yun Zhao, Jiling Wen, Sheng Liu, Tianhe Huang, Ishita Hatial, Xiaoxia Peng, Hawraa Al Janabi, Gang Huang, Jackson Mittlesteadt, Michael Cheng, Atul Bhardwaj, Brandon L. Ashfeld, Kenneth R. Kao, Dean Y. Maeda, Xing Dai, Olaf Wiest, Brian S.J. Blagg, Xuemin Lu, Liang Cheng, Jun Wan, Xin Lu
Journal: Science Immunology (2023)

The noninflamed microenvironment in prostate cancer represents a barrier to immunotherapy. Genetic alterations underlying cancer cell-intrinsic oncogenic signaling are increasingly appreciated for their role in shaping the immune landscape. Recently, we identified Pygopus 2 (
Tumor-Induced Neovascularization in the Mouse Eye&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: V. R. Muthukkaruppan, L. Kubai, R. Auerbach
 6
Journal: JNCI Journal of the National Cancer Institute (1982)

Journal Article Tumor-Induced Neovascularization in the Mouse Eye Get access V. R. Muthukkaruppan, V. R. Muthukkaruppan Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Kubai, L. Kubai Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Auerbach R. Auerbach 6 6Address reprint requests to Dr. Auerbach. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 69, Issue 3, September 1982, Pages 699–708, https://doi.org/10.1093/jnci/69.3.699 Published: 01 September 1982 Article history Received: 11 December 1981 Accepted: 30 March 1982 Published: 01 September 1982
Is Acceptance and Commitment Therapy Superior to Established Treatment Comparisons?
Authors: Michael Levin, Steven C. Hayes
Journal: Psychotherapy and Psychosomatics (2009)

Letters| September 08 2009 Is Acceptance and Commitment Therapy Superior to Established Treatment Comparisons? Subject Area: Psychiatry and Psychology Michael Levin; Michael Levin University of Nevada, Reno, Nev., USA Search for other works by this author on: This Site PubMed Google Scholar Steven C. Hayes Steven C. Hayes University of Nevada, Reno, Nev., USA Search for other works by this author on: This Site PubMed Google Scholar Psychother Psychosom (2009) 78 (6): 380. https://doi.org/10.1159/000235978 Article history Published Online: September 08 2009 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Michael Levin, Steven C. Hayes; Is Acceptance and Commitment Therapy Superior to Established Treatment Comparisons?. Psychother Psychosom 1 September 2009; 78 (6): 380. https://doi.org/10.1159/000235978 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsPsychotherapy and Psychosomatics Search Advanced Search This content is only available via PDF. © 2006 S. Karger AG, Basel2009Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Article PDF first page preview Close Modal You do not currently have access to this content.
Microbiological investigation of a hospital outbreak of invasive group A streptococcal disease in Krakow, Poland
Authors: M. Strus, A. Drzewiecki, A. Chmielarczyk, A. Tomusiak, P. Romanek, K. Kosowski, P. Kochan, M. van der Linden, R. Lütticken, P.B. Heczko
Journal: Clinical Microbiology and Infection (2010)
A Double‐Blind, Multicenter Immunotherapy Trial in Children, Using a Purified and Standardized <i>Cladosporium herbarum</i> Preparation I. Clinical Results
Authors: S. Dreborg, B. Agrell, T. Foucard, N.‐I. M. Kjellman, A. Koivikko, S. Nillson
Journal: Allergy (1986)

A double‐blind histamine placebo controlled immunotherapy trial was performed to investigate the clinical effect of a purified and standardized Cladosporium herbarum allergen preparation. Thirty children with a clinical history suggesting mould‐induced asthma and/or rhinoconjuctivitis were included. The diagnosis was confirmed by positive skin prick test and Phadebas RAST® as well as positive bronchial and/or conjunctival provocation test to Cladosporium herbarum . Immunotherapy was given for 10 months in a double‐blind manner to randomized groups with either Pharmalgen®/ Cladosporium herbarum preparation or histamine placebo. Allergic side effects to injections were common, especially during the peak of the mould season (July‐September in Scandinavia). In the active group, 13/16 patients experienced general reactions during the first 10 months of treatment. After 6 months of treatment, eye, nose and bronchial symptom scores and peak expiratory flow rates were similar for the groups, maybe because most of the children were also sensitive to many other allergens, including Alternaria alternala . However, medication scores were significantly lower in the treated group ( P &lt; 0.01). Bronchial ( P &lt; 0.01) and conjunctival sensitivity ( P = 0.01) were significantly reduced in the Cladosporium ‐treated group but not in the placebo group after 10 mouths of treatment. This is the first double‐blind clinical trial showing the clinical efficacy of immunotherapy in children with mould‐induced asthma.
Mouse Mammary Tumor Virus-like RNA Transcripts and DNA Are Found in Affected Cells of Human Breast Cancer
Authors: Caroline E. Ford, Margaret Faedo, William D. Rawlinson
Journal: Clinical Cancer Research (2004)

Abstract Identifiable risk factors for the development of breast cancer include age, diet, family history, and lifetime estrogen exposure. An infectious agent (mouse mammary tumor virus; MMTV) is known to cause murine breast tumors and may be involved in the pathogenesis of human disease. Multiple studies have detected MMTV-like sequences in 30 to 60% of breast cancer samples and up to 1.8% of samples from normal breast. Using in situ PCR of MMTV-like sequences of formalin-fixed, paraffin-embedded breast tissue, viral sequences have been located in cancerous epithelial cells in breast acini of male and female breast tumors, but not in adjacent nonmalignant cells. MMTV-like sequences were also located in the epithelial cells of male gynecomastia samples. Using reverse transcriptase in situ PCR, RNA transcripts from the env gene were also detected within cancerous epithelial cells of 78% of DNA-positive tumors, 80% of gynecomastia samples, and 0% of normal tissues screened. This suggests the virus may be replicating in these cells. The epidemiologic and histopathological data are consistent with the association of an MMTV-like virus with breast cancers in men and women. The association with gynecomastia, a benign, possibly premalignant condition suggests hormonal influences, rather than cancer per se, may be the dominant factor in determining viral presence and replication.
The 2003 heat wave
Authors: J- P Sardon
Journal: Eurosurveillance (2007)

The July-August 2005 issue of Eurosurveillance focused on the impact on mortality of the 2003 heat wave in Europe, with articles that were based on various methods and looked at different time periods. The subject of this letter is to assess, using a unique methodology, the excess mortality related to the 2003 heat wave across the continent.
The Social Construction of the Human Brain
Authors: Leon Eisenberg
Journal: American Journal of Psychiatry (1995)

Objective: The purpose of this article is to review the development of concepts about the contribution of nature and nurture to brain structure and mental function, and to derive the implications of these changing concepts for clinical practice. Method: The literature of the past five decades, as refracted by the author's personal experience in academic psychiatry during that interval, is reviewed. Results: Psychiatric theory has swung through mighty arcs in recent years but has begun to re-equilibrate. Fifty years ago, psychoanalysis dominated the academic scene; for the past two decades, reductionist biological determinism has held the fort. Neither position is tenable. To subscribe to either is possible only by ignoring conflicting evidence. Worse, it means short-changing patients, whose disorders do not come neatly packaged into "organic" and "functional" compartments. Development is neither predestined in the genome nor completely malleable to shaping by the environment. Children inherit, along with their parents' genes, their parents, their peers, and the communities they inhabit. Conclusions: Contemporary psychiatric research conclusively demonstrates that mind/brain responds to biological and social vectors and is jointly constructed by both. Major brain pathways are specified in the genome; detailed connections are fashioned by, and consequently reflect, socially mediated experience in the world. Just at the time when integration at the level of theory is coming into sight, comprehensive patient care is endangered by for-profit corporate managed care, which is transforming medical visits into commodities on a production line. Physicians and patients must join in a coalition to protect quality, ensure access, and build continuity into all of medical care.
Plasma High-Density Lipoprotein Cholesterol Level
Authors: Stephen B. Hulley
Journal: JAMA (1977)

Determinants of circulating high density lipoproteins (HDL) were sought in 301 men studied during a year of participation in a coronary prevention program. Mean plasma HDL-cholesterol concentration rose by 2.8 mg/dl (6%) in the group receiving multifactor intervention, but the change did not differ significantly from that in the comparison group. Larger changes in both directions were seen in many individuals. Multiple regression analysis of these changes indicates that increased plasma HDL levels occur when plasma triglyceride level is decreased, cigarette smoking is reduced, and habitual alcohol intake is increased. Increases in the concentration of HDL-cholesterol also tended to accompany adherence to the fat-controlled diet, reduction in LDL-cholesterol level, and loss of body weight. Conventional coronary prevention programs are unlikely to have an adverse influence on this new, risk-lowering factor. (<i>JAMA</i>238:2269-2271, 1977)
Disuse and Aging
Authors: Walter M. Bortz
Journal: JAMA (1982)

A review of biologic changes commonly attributed to the process of aging demonstrates the close similarity of most of these to changes subsequent to a period of enforced physical inactivity. The coincidence of these changes from the subcellular to the whole-body level of organization, and across a wide range of body systems, prompts the suggestion that at least a portion of the changes that are commonly attributed to aging is in reality caused by disuse and, as such, is subject to correction. There is no drug in current or prospective use that holds as much promise for sustained health as a lifetime program of physical exercise. (<i>JAMA</i>1982;248:1203-1208)
The Sanitary State of Rome
Authors: L. Aitken
Journal: BMJ (1873)

Surgeon in the Coldstream Guards.So numerous have been the cases of late years of successful treatment of aneurism by compression, that it seems almost unnecessary to add to the number; but, as there were in this case a few points of special interest, I think it as well to bring it before the notice of the profession.Serjeant S., aged 39, twenty years in the service, was admitted into hospital on May 23rd, 1872, for a pulsating tumour about the size of an orange, situated on the inner side of the front of the thigh imme- diately over Hunter's canal, and extending slightly also into the pop- liteal space.The patient stated that the swelling first appeared three months before his admission, after running up and down stairs a great deal on duty; but he did not take any particular notice of it until very recently, when, after a fortnight's duty at Aldershot, which involved much marching, the pain in the tumour and along the front of the leg became so great that he was obliged to report himself sick.He was of slight build, and nervous temperament, but a healthy man and of steady habits.The following day, a double femoral compressor was put on the thigh, and the pulsation of the aneurism was readily arrested.From that date to July 2nd (nearly six weeks) this instrument was constantly applied without any beneficial result, beyond, perhaps, developing the
Improvement in Bronchial Squamous Metaplasia in Smokers Treated With Folate and Vitamin B12
Authors: Douglas C. Heimburger
Journal: JAMA (1988)

To test whether changes in folate and vitamin B<sub>12</sub>nutrition modify the severity of potentially premalignant lesions identified by cytology in sputum samples of smokers, we conducted a randomized, controlled prospective intervention trial in smokers with bronchial squamous metaplasia. Seventy-three men with a history of 20 or more pack-years of cigarette smoking who had metaplasia on one or more sputum samples were stratified according to smoking level and randomly assigned to four months' treatment with either placebo or 10 mg of folate plus 500 μg of hydroxocobalamin. Direct cytological comparison of the two groups after four months showed significantly greater reduction of atypia in the supplemented group. This provides preliminary evidence that atypical bronchial squamous metaplasia may be reduced by supplementation with folate and vitamin B<sub>12</sub>. However, the significance of these findings is tempered by substantial spontaneous variation in sputum cytologies, the small study population, the short duration of the trial, and the supraphysiological doses of folate and B<sub>12</sub>used. The results should not be construed as pointing to a potential way of preventing lung cancer in individuals who continue to smoke or as supporting self-medication with large doses of folate or B<sub>12</sub>by smokers. (<i>JAMA</i>1988;259:1525-1530)
OCCURRENCE OF γ-GLOBULIN COMPLEXES IN SERUM AND JOINT FLUID OF RHEUMATOID ARTHRITIS PATIENTS: USE OF MONOCLONAL RHEUMATOID FACTORS AS REAGENTS FOR THEIR DEMONSTRATION
Authors: R. J. Winchester, H. G. Kunkel, V. Agnello
Journal: The Journal of Experimental Medicine (1971)

γG globulin complexed in an unusual form has been demonstrated in the serum of many patients with rheumatoid arthritis. Such complexes have been detected and isolated principally through precipitation reactions with monoclonal γM rheumatoid factors. These monoclonal rheumatoid factors exhibited a greater sensitivity to react with small complexes or aggregates of γ-globulin than polyclonal rheumatoid factor from rheumatoid arthritis sera or isolated C1q. The serum complexes consisted in large part of high molecular weight but acid-dissociable 7S γG globulin molecules They however differed from the complexes in the joint fluid by not yielding precipitates with C1q and were not found in association with evidence of marked serum complement fixation or activation. A small number of systemic lupus erythematosus sera, primarily those forming cryoprecipitates, also gave reactions with monoclonal rheumatoid factor. Sera from patients with a variety of nonrheumatic diseases gave a low incidence of reactions. The exact nature of the complexes in the rheumatoid arthritis sera remains somewhat in doubt although γG rheumatoid factors appear partly involved.
Dose dependent response of symptoms, pituitary, and bone to transdermal oestrogen in postmenopausal women.
Authors: P L Selby, M Peacock
Journal: BMJ (1986)

The effect of the plasma oestradiol concentration on climacteric symptoms, gonadotrophin release, and bone resorption was studied in three groups of postmenopausal women given 0.025 mg, 0.05 mg, or 0.1 mg transdermal oestradiol daily. There was a dose related reduction in symptoms, plasma follicle stimulating hormone concentration, and urinary calcium and hydroxyproline excretion. The relation of the response to plasma oestradiol values was similar for each variable with an initial large reduction and little change in response to increases in the plasma oestradiol concentration above 150 pmol/l (41 pg/ml). Hormone replacement therapy producing an effect equivalent to higher oestradiol concentrations is likely to increase the risk of side effects without conferring any additional benefit.
Appointment Reminders to Reduce No-Show Rates
Authors: JudyAnn Bigby
Journal: JAMA (1983)

To determine whether reminders are cost-effective for an adult primary care internal medicine center, we randomized 590 scheduled, follow-up appointments to no reminder, computer-generated letter reminders, and telephoned reminders. The no-show rate was reduced from 24% in the control group to 14% in the reminder groups, and letter and telephoned reminders were equally effective. An economic analysis showed that about two thirds of the savings realized from reminders was generated in 23% of the patients whose prior predicted probability of a no-show appointment was above 20%. However, in our primary care center, computer-generated letter reminders were estimated to be cost-effective whenever the probability of a no-show was above 5%, and telephoned or manual letter reminders were estimated to be cost-effective whenever the probability of a no-show was above about 11%. Based on our sensitivity analysis, telephoned or manual letter reminders should be cost-effective in many other ambulatory settings as well, although in some settings, reminders may be restricted to patients at high risk for no-show behavior. (<i>JAMA</i>1983;250:1742-1745)